rs258226

Positions:

• chr5-14801957-A-G
• chr5-14801957-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054027.6(ANKH):​c.97-32766T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,096 control chromosomes in the GnomAD database, including 30,603 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30603 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

Genes affected

ANKH (HGNC:15492): (ANKH inorganic pyrophosphate transport regulator) This gene encodes a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. Progressive ankylosis-mediated control of pyrophosphate levels has been suggested as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals. Mutations in this gene have been associated with autosomal dominant craniometaphyseal dysplasia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.97-32766T>C		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.97-32766T>C		intron_variant			XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.97-32766T>C		intron_variant		1	NM_054027.6	ENSP00000284268	P1
ANKH	ENST00000513115.1	n.122-32766T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95667 AN: 151978 Hom.: 30536 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.630 AC: 95801 AN: 152096 Hom.: 30603 Cov.: 32 AF XY: 0.636 AC XY: 47261 AN XY: 74348

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.583

Alfa AF: 0.624 Hom.: 4704

Bravo AF: 0.633

Asia WGS AF: 0.781 AC: 2715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs258226; hg19: chr5-14802066;